Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

One of the major difficulties in the treatment of Parkinson's disease with L-Dopa alone or associated with a decarboxylase inhibitor lies in the frequent occurrence of involuntary movements. In some cases these movements can be prevented (eliminated) by increasing the plasma DCI concentration or by associating 3-oxy-methyl-dopa. In resistant cases the authors have conducted a trial with EP 19-088, which belongs to a new class of tricyclic derivatives of indenopyridine. The trial population comprised 42 patients. In 12 of these there was complete cessation of symptoms. In 9 patients a marked improvement was noted, while in 10 others the improvement was slight but definite. The treatment was discontinued in 2 cases due to episodes of increased confusion. In the other 9 patients the experimental treatment had no effect. No side effects were observed in 24 of the 42 patients tested. In addition to symptoms such as nausea or transient heartburn, the remaining patients reported either a slight worsening of their parkinsonian symptoms or an increase in diurnal fatigability.
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PMID:[Abnormal movements induced by L-dopa. New therapeutic possibilities]. 112 79

Several hypotheses have explained the beneficial effect of adding bromocriptine (BR) to levodopa (LD) in Parkinson's disease (PD) by interaction at the striatal level. In the present study we show the influence of BR on plasma LD values in an acute loading experiment (125 mg LD + 12.5 mg carbidopa [DCI] given alone and together with 2.5 mg BR at 0 time; 4 h observation). On the basis of this influence we have been able to differentiate between three groups of patients: (a) in six patients (five of them with frequent off episodes) LD values were significantly lower (p less than 0.05) when both drugs were given together (area under the curve [AUC] +/- SE 2.10 +/- 0.42 micrograms/ml/h vs. 4.96 +/- 1.10 micrograms/ml/h); (b) in eight patients (one with frequent akinesia) LD levels were significantly higher (p less than 0.003) when both drugs were given together (AUC +/- SE 4.05 +/- 0.51 micrograms/ml/h vs. 1.94 +/- 0.19 micrograms/ml/h); (c) in six patients (without motor fluctuations) no difference in LD levels was noted (AUC +/- SE 3.91 + 0.62 micrograms/ml/h vs. 3.81 +/- 0.70 micrograms/ml/h). The clinical evaluation (Webster scale) did not show substantial differences, except for increased dyskinesia, which correlated with higher LD levels. In summary, we suggest that the diminution of motor fluctuations and the occurrence of dyskinesias when BR is added to LD may stem from changes in LD plasma levels. These findings would be taken into consideration in the interpretation of therapeutic response fluctuations under combined treatment.
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PMID:The influence of bromocriptine on the pharmacokinetics of levodopa in Parkinson's disease. 177 22

We recently demonstrated that when different drugs (mainly used for the treatment of Parkinson's disease) are administered in combination they interfere with the availability of bromocriptine in the brain of rats (striatum and hypothalamus). In the present study performed with parkinsonian patients, we measured plasma levels of bromocriptine (RIA) over 4 h after giving orally 5 mg bromocriptine alone; together with levodopa 250 mg plus 25 mg DCI (10 patients); with 100 mg amantadine HCl (5 patients) and with biperiden 5 mg (5 patients). Amantadine and biperiden did not interfere with the pharmacokinetics of bromocriptine. However, levodopa significantly diminished plasma levels (a mean increment of 1.78 mg +/- 0.30 vs 0.92 +/- 0.18 mg/ml). We postulate that levodopa may interfere with the metabolism of bromocriptine in the liver. Although we did not observe substantial clinical differences among the patients (Webster scale), this study supports our previous findings and suggests that one of the advantages of combined treatment may result from a modification of the plasma levels of bromocriptine by levodopa. A "smoothing" of the plasma bromocriptine curve possibly avoids sudden oscillations of the drug availability and enables a more "stable" penetrability of the medication into the central nervous system.
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PMID:Bromocriptine blood levels after the concomitant administration of levodopa, amantadine and biperiden in Parkinson's disease. 237 43

The administration of bromocriptine in addition to levodopa in Parkinson's disease produces beneficial results. Several hypotheses have explained the advantage of the combined treatment by a pharmacodynamic interaction in the striatum. However, no study has considered the possibility that levodopa modifies the kinetics of bromocriptine. In the present study performed with parkinsonian patients, we measured blood levels of bromocriptine (by radioimmunoassay) at 0, 30, 60, 90, 120, 180, and 240 min after the oral administration of bromocriptine alone and together with 250 mg levodopa plus 25 mg DCI. After loading of bromocriptine alone, we found mean peak levels at 60 min (1.42 ng/ml) and at 90 min (1.82 ng/ml). These values were reduced by levodopa (0.97 ng/ml at 60 min and 0.93 ng/ml at 90 min). Although we did not observe substantial clinical differences among the groups after the drug challenge (Webster scale), this study supports our previous findings and suggests that one of the advantages of a combined treatment may result from a modification of the plasma levels of bromocriptine by levodopa. A "smoothing" of the plasma bromocriptine curve possibly avoids sudden oscillations of the drug and enables a more "stable" penetrability of the medication into the central nervous system. Therefore long-term combined treatment is advised in preference to bromocriptine alone.
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PMID:The influence of levodopa in the pharmacokinetics of bromocriptine in Parkinson's disease. 261 67

L-threo-3,4-dihydroxyphenylserine (L-threo-DOPS) was administered at a maintenance dose of 600-900 mg/day, in 10 patients with Parkinson's disease who exhibited a notable freezing phenomenon under the medication of L-DOPA/DCI (DOPA-decarboxylase inhibitor). Changes in clinical symptoms were examined after 8 weeks of treatment. Frozen gait and dysarthria were markedly alleviated by L-threo-DOPS administration, and the rigidity persisting under conventional medication was also relieved. Marked improvement in frozen gait was observed in 1-2 weeks, and that of dysarthria in 2-3 weeks, after the initiation of L-threo-DOPS administration. Nine of the 10 patients were treated with a combination of DOPA and DCI, and the L-threo-DOPS/benserazide ratio and L-threo-DOPS/carbidopa ratio were 9.2 and 26.3, respectively. The effect of L-threo-DOPS were enhanced in one patient in whom DCI was changed from carbidopa to benserazide, suggesting the necessity of further studies on the type and dose of DCI to be combined with L-threo-DOPS.
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PMID:L-threo-3, 4-dihydroxyphenylserine treatment of Parkinson's disease. 393 72

Aim of this study was the characterization of the circadian melatonin profile in de novo Parkinson patients (N = 9, age 60.0 +/- 3.2 years, mean +/- SEM) and the comparison of these profiles with those of controls and Parkinson patients treated with l-dopa/decarboxylase inhibitor (l-dopa/DCI). We collected 14 venous blood samples during a period of 24 hours and measured the serum melatonin levels by a radioimmuno assay. De novo Parkinson patients displayed the nocturnal melatonin peak (acrophase) at the same time as controls and significantly later than l-dopa/DCI treated patients (1:54 +/- 15.6 min [average clock time +/- SEM in minutes] vs. 1:45 +/- 15.6 min vs. 0:13 +/- 40.8 min). The amount of secreted melatonin did not differ among the three groups. Stage and duration of Parkinson's disease did not correlate with the amount of secreted melatonin. Patients of the tremor subgroup, however, secreted more melatonin than patients presenting only with rigidity and akinesia. The phase advance in Parkinson patients treated with l-dopa/DCI is possibly due to a central nervous dopaminergic effect elicited by l-dopa administration and not inherent to Parkinson's disease per se.
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PMID:Circadian secretion pattern of melatonin in de novo parkinsonian patients: evidence for phase-shifting properties of l-dopa. 836 2

Tolcapone is a potent, reversible inhibitor of catechol O-methyltransferase (COMT) intended for use as an adjunct to levodopa therapy for Parkinson's disease (PD). Findings from the first pharmacokinetics/pharmacodynamics and tolerability studies of tolcapone in volunteers are reviewed. Following linear and dose-proportional pharmacokinetics, tolcapone is rapidly absorbed and eliminated after single- or multiple-dose (i.e., tid) administration. Onset of COMT inhibition is rapid, substantial, and reversible, and is not affected by the co-administration of levodopa/decarboxylase inhibitor (levodopa/DCI). When given together with levodopa/DCI, tolcapone increases the relative bioavailability and plasma elimination half-life of levodopa, without affecting its peak plasma concentration. This leads to more stable plasma levels of levodopa, and the formation of 3-O-methyldopa is effectively reduced. Tolcapone was well tolerated alone or in combination with levodopa/DCI, and the results indicated that the effective dose in patients with PD would be in the range of 50-400 mg tid.
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PMID:Pharmacokinetics, pharmacodynamics, and tolerability of tolcapone: a review of early studies in volunteers. 959 20

During the last half of the 20th century, medical treatment for Parkinson's disease (PD) showed remarkable progresses, resulting in marked prolongation of life and self-dependency of patients. In Japan, peak of ages of PD patients visiting all medical institutions was between 75 and 84 years of age(1993), with which course of illness is predicted to exceed twenty years in a large number of patients. As exploration of neuroprotective therapies for PD has not been successful yet, continuous progress in neuronal cell death in the substantia nigra result in loss of efficacy of medication, motor fluctuations and CNS side effects such as dyskinesia and psychosis in the long course of dopaminergic supplementation therapies. Future development of medical therapies for PD is expected in different ways. First, elaboration in controlled-release of DCI/levodopa, utilization of dopamine(DA) receptor agonists with different profiles in affinity to DA receptor subtypes and half-time of blood concentration, and utilization of COMT inhibitors. Second, neuroprotection with MAO-B inbitators or DA receptor agonists. Neuroprotective function is expected in animal studies for these substances but clinical usefulness should be verified with randomised controlled trials. Third, treatment for extra-motor symptoms such as dementia, cognitive disorders, depression, autonomic disturbances such as orthortatic hypotension and bladder disturbances, which is essential for maintenance of quality of life of patients with long course of illness. Gene therapy, neuroprotection before development of symptoms in PD may be attained within the first few decades of the next century. In this respect, establishment of preclinical diagnosis with neuroimaging and sensitive motor and psychological tests is imperative.
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PMID:[A prospect of treatment for Parkinson's disease in the 21st century]. 1106 33

Tremor is the most common initial symptom and one of the cardinal features of Parkinson's disease. Mild tremor causes only minimal disability, but severe tremor causes more significant disability and distress for the patient than rigidity and/or bradykinesia. Anticholinergic agents, levodopa/DCI and dopamine agonists are most common and beneficial in parkinsonian tremor, but efficacies of these medications are variable among patients. Rigidity and bradykinesia are more responsive to levodopa/DCI therapy than tremor. Clozapine is an atypical neuroleptic agent, not on the market in Japan, and has been reported to decrease or ameliorate parkinsonian tremor through the studies of open label and double blind crossover as a new drug for parkinsonian tremor.
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PMID:[Pharmacological treatment of parkinsonian tremor]. 1106 52

We report a case of Parkinson's disease (PD) diagnosed by REM sleep behavior disorder (RBD). The patient was a 68-year-old man. On admission, rigidity in the left upper and lower extremities, bradykinesia, and gait disturbance were noted. In addition, polysomnography revealed REM sleep without atonia (RWA), and a diagnosis of untreated PD associated with RBD was made. Polysomnographic data showed that REM density decreased and RWA tended to increase after administration of a combination of L-DOPA and DCI (L-DOPA/DCI). Thus, we considered that the pathophysiological mechanism of RBD in this case was based not only on the dysfunction of the brainstem mechanism of RWA, but also on the impairment of dopaminergic neuron.
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PMID:Parasomnia as an occasion for the diagnosis of Parkinson's disease. 1142 72


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